Endometriosis-derived iPSCs reveal conserved stromal maturation and endocrine responsiveness

Here, we establish an induced pluripotent stem cell (iPSC)–based platform derived from patients with endometriosis to model endometrial stromal differentiation in a controlled human context. Using a defined differentiation framework, endometriosis-derived iPSCs transition from pluripotency through mesenchymal commitment toward stromal-like states and acquire transcriptional hormone responsiveness.

Trajectory-resolved transcriptomic analyses reveal coordinated repression of pluripotency and proliferative programs with induction of stromal lineage signatures. Benchmarking against independent bulk transcriptomic datasets demonstrated that in vitro–derived stromal cells progressively acquired gene expression profiles that resembled eutopic endometrial stromal programs in endometriosis. To explore potential functional consequences, conditioned media from iPSC-derived stromal cells was applied to THP-1 macrophage-like cells, revealing coordinated transcriptional reprogramming.